Despite all efforts at management, prognosis of advanced lung cancer is extremely poor, with a median survival time of ~1 year. The number of cancer patients aged >70 years is significantly increased among the cancer patient population. The aim of this study was to investigate the clinical importance of age in lung cancer. Data from 110 patients with histologically confirmed lung cancer, who were treated and followed up in the Institute of Oncology, University of Istanbul, were recorded from medical charts. There were 100 (91%) males with a median age of 59 years (range, 35–88 years). The majority of patients had non-small cell lung cancer (NSCLC; 84%) and metastatic stage (56%). The rate of positive response to chemotherapy was lower in elderly patients (P=0.01) and the incidence of anemia was higher compared with that in younger patients (P=0.02). The majority of mortalities occurred in elderly patients (P=0.01). The median survival time of elderly patients was significantly lower compared with that of younger patients (37.8 vs. 57 weeks; P=0.009). The 1-year survival rates in younger and elderly patients were 67.3 and 42.5%, respectively. In multivariate analysis, elderly patients also had significantly poorer survival (P=0.023). In the group of elderly patients, analyses revealed that significant prognostic factors, including stage of disease and serum lactate dehydrogenase (LDH) levels, were associated with survival. Elderly patients diagnosed with small cell lung cancer had a poorer outcome compared with those with NSCLC (P=0.009), and older patients with elevated serum LDH levels had a shorter survival time compared with those with normal levels (P=0.042). In conclusion, age is one of the major prognostic factors affecting survival in lung cancer patients; therefore, patients should be managed according to age in clinical practice.
Currently, lung cancer is a major health problem. In the USA, an estimated 222,500 new cases of lung cancer were diagnosed and 157,300 mortalities occurred due to the disease in 2010 (
The prognosis of lung cancer remains poor. Up to 85% of patients are diagnosed at an advanced stage. Despite all efforts at management, prognosis of lung cancer patients is unsatisfactory, with a median survival of ~1 year and a 5-year survival rate of only 16% (
Cancer is one of the five leading causes of mortality in all age groups among males and females; it is the leading cause of mortality among men and women aged 40–79 years (
Age has been recognized as a prognostic factor in multiple cancers treated with definitive intent. In addition to numerous variables that have been reported to be significant prognostic factors in lung cancer, several studies have demonstrated that age is an important independent prognostic factor affecting survival of patients (
This study included 110 consecutive patients admitted to the Institute of Oncology, University of Istanbul (Turkey) with histologically or cytologically confirmed non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) who were treated and followed up in our clinic; data were recorded from medical charts. Patients with bidimensional measurable disease without a history of chemo- or radiotherapy in the last six months were included in the study. The staging of metastatic patients was performed using various imaging modalities, including computed tomography (CT), magnetic resonance imaging and positron emission tomography/CT. The pathological diagnosis of lung cancer was established in accordance with the revised World Health Organization classification of lung tumors (
The pretreatment evaluation included detailed clinical history and physical examination with a series of biochemical tests, and complete blood cell counts. Those with Eastern Cooperative Oncology Group PS ≤2 and appropriate blood chemistry tests received chemotherapy on an outpatient basis comprising platinum compounds with or without radiotherapy, depending on the stage of disease. Patients were treated with various chemotherapy regimens as a single agent or combination therapy. Regimens of single or combination chemotherapy were selected based on the PS of patients and extension of disease. Drug schemes consisted of platinum agents in combination with newer cytotoxic drugs, including paclitaxel, docetaxel, gemcitabine and vinorelbine.
Response to chemotherapy was evaluated radiologically following two to three cycles of chemotherapy according to international criteria, the revised Response Evaluation Criteria in Solid Tumors guidelines (version 1.1). Non-responders to chemotherapy and relapsed patients were treated with second-line chemotherapy if they had a good PS. Chemotherapy was continued until disease progression or unacceptable toxicity. Follow-up programs consisted of clinical, laboratory and radiological assessments performed at 8-week intervals during chemotherapy or every 12 weeks for patients receiving no anticancer treatment.
Continuous variables were categorized using median values as the cut-off point. Assessment of correlations and comparisons between various clinical/laboratory parameters was performed using Mann-Whitney U test and Kruskal-Wallis test for 2 and 3 groups, respectively. Survival was calculated from the date of first admission to hospital to mortality resulting from any cause or to last contact with the patient or any family member. The Kaplan-Meier method was used for estimation of survival distribution and differences in survival were assessed by the log-rank statistic. Multivariate survival analysis was performed using Cox’s proportional hazards regression model. P<0.05 was considered to indicate a statistically significant difference. Statistical analysis was performed using SPSS 16.0 software (SPSS Inc., Chicago, IL, USA).
Demographic, laboratory and clinicopathological features of patients are listed in
The distribution of prognostic factors according to the age of patients was generally similar (
The median follow-up time was 20.3 weeks (range, 4.4–72.6 weeks). At the time of analysis, 31 patients (19.4%) had succumbed due to disease-related or unrelated factors. The median survival time of patients was 57 weeks (95% CI, 45.6–68.3 weeks). The 1-year survival rate was 55.1±7.7%. In the subset analysis, it was identified that 40% of elderly and 17% of younger patients succumbed to the disease. The median survival time of elderly patients (37.8 weeks; 95% CI, 11.6–64.0) was significantly lower than that of younger patients (57 weeks; 95% CI, 45.8–68.1) (P=0.009). The 1-year survival rates in younger and elderly patients were 67.3±11.3 and 42.5±1.0%, respectively (
In the univariate analyses, elderly patients had poorer outcomes compared with younger patients (P=0.009;
Due to increasing life expectancy and the increased risk of cancer with aging, lung cancer is common in elderly individuals. More than half of lung cancer cases are diagnosed in patients aged >65 years (
Treatment of elderly patients with lung cancer poses a huge challenge (
Elderly patients included in clinical trials in which younger patients are also included, represent a highly selective population of patients, as they must satisfy extremely strict inclusion criteria. Thus, the results obtained cannot be extrapolated to the whole population of elderly patients (
Studies performed on elderly patients with various malignancies show that elderly patients benefit from chemotherapy to a similar extent as younger patients, with manageable side-effects (
Commonly used guidelines of oncology [American Society of Clinical Oncology (ASCO) and European Organization for Research and Treatment of Cancer (EORTC)] are based on subgroup analyses of elderly patients included in non-elderly dedicated trials, which is why specific studies dedicated to elderly patients should be conducted and elderly patients should be interpreted differently in clinical practice. Notably, several phase III trials specifically dedicated to elderly patients with advanced NSCLC have been performed (
Age should not be criteria of choice for the best treatment due to the ASCO recommendations in 2009 (
Moreover, there have been no specific trials concerned with salvage chemotherapy for elderly NSCLC patients. The only available study is a subgroup analysis of 86 patients aged ≥70 years among the total 571 patients included in a phase III study comparing pemetrexed and docetaxel as a second-line therapy (
Toxic events with chemotherapy are more common in elderly patients. Alterations of physiological functions, particularly renal and hematopoietic functions, with aging may explain increased chemotherapy toxicity in elderly patients (
PS is a major prognostic factor of survival in lung cancer patients and is also a guide for the most appropriate treatment of advanced NSCLC. PS, which provides a useful guide in making treatment decisions for younger patients, is often insufficient to assess the overall status of elderly patients (
In this study, we demonstrated that age is one of the major prognostic factors affecting survival in lung cancer patients. The rate of mortality was higher in elderly patients; thus, the median survival time of elderly patients was significantly lower compared with that of younger patients in univariate and multivariate analyses. Elderly patients diagnosed with SCLC histology had poorer outcomes compared with those with NSCLC, and older patients with elevated serum LDH levels had shorter survival times compared with those with normal levels. Additionally, elderly patients were found to be more anemic and less responsive to chemotherapy compared with younger patients. However, when older and younger groups were assessed separately, the impact of chemotherapy responsiveness on survival did not differ, suggesting that the disparity of survival between younger and older groups was not associated with chemotherapy response rate.
In terms of criticisms of the present study, we were unable to analyze the mortality as a result of unrelated reasons apart from cancer and their comorbidities. The chemotherapy regimens and toxicity rates were not compared in the present study, as our aim was only to show the significance of age on survival in association with the administration of chemotherapy and other probable prognostic factors. Despite these limitations, this study is important, as data investigating the outcomes of lung cancer in elderly patients and the effect of age on survival in lung cancer is limited.
In conclusion, almost all patients with advanced lung cancer have a poor prognosis. Establishing clear prognostic variables during initial diagnosis may help physicians to decide which patients should be considered for supportive care only, single agent chemotherapy, combination chemotherapy or multimodality treatment options. In this study we demonstrated that the age of patients is one of the major prognostic factors affecting survival in lung cancer patients. Age alone should not preclude these patients from receiving chemotherapy. Treatment decisions should be based on physiological rather than chronological age. Factors that require evaluation in elderly patients include functional status, comorbidity and cognition.
Overall survival of patients with lung cancer according to age of patients (P=0.009).
Patient characteristics and distributions of parameters according to patient age.
Parameters | All patients, % (n=110) | <60 years, % (n=57) | ≥60 years, % (n=53) | P-value |
---|---|---|---|---|
Patients | 100 | 52 | 48 | |
Gender | 0.32 | |||
Male | 91 | 88 | 94 | |
Female | 9 | 12 | 6 | |
Histology | 0.19 | |||
NSCLC | 84 | 81 | 89 | 0.26 |
Adeno | 30 | 25 | 36 | |
Squamous | 26 | 23 | 30 | |
Other (unclassified) | 28 | 33 | 23 | |
SCLC | 16 | 19 | 11 | |
Stage of disease | ||||
NSCLC | 0.41 | |||
Local (stage I+II) | 6 | 4 | 11 | |
Locally advanced (stage III) | 33 | 44 | 34 | |
Metastatic (stage IV) | 45 | 52 | 55 | |
SCLC | 0.40 | |||
Limited | 5 | 36 | 17 | |
Extensive | 11 | 64 | 83 | |
Serum hemoglobin level | ||||
Low (<11.9 g/dl) | 29 | 19 | 39 | |
Normal (≥12 g/dl) | 71 | 81 | 61 | |
Serum WBC count | 0.20 | |||
Normal (<10,999) | 77 | 72 | 82 | |
Elevated (≥11,000) | 23 | 28 | 18 | |
Serum platelet count | 0.65 | |||
Normal (<349,000) | 65 | 63 | 67 | |
Elevated (≥350,000) | 35 | 37 | 33 | |
Erythrocyte sedimentation rate (/h) | 0.14 | |||
Normal (<40) | 45 | 38 | 53 | |
Elevated (≥41) | 55 | 62 | 47 | |
Serum LDH level | 1.00 | |||
Normal (<449 U/l) | 75 | 75 | 75 | |
Elevated (≥450 U/l) | 25 | 25 | 25 | |
Response to chemotherapy | ||||
Yes | 47 | 68 | 37 | |
No | 53 | 32 | 63 | |
Final status | ||||
Alive | 72 | 83 | 60 | |
Succumbed | 28 | 17 | 40 |
Significant P-values (<0.05) are highlighted in bold. NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; WBC, white blood cell; LDH, lactate dehydrogenase.
Univariate and multivariate analyses of survival and clinical and laboratory variables.
Variables | Univariate analysis P-value | Multivariate analysis P-value |
---|---|---|
Age (<60 vs. ≥60 years) | ||
Gender (female vs. male) | 0.415 | 0.690 |
Histology (NSCLC vs. SCLC) | 0.446 | 0.104 |
Stage of disease (non-metastatic vs. metastatic) | 0.109 | |
LDH (<450 vs. ≥450 IU/l) | 0.263 | |
Hemoglobin (<12 vs. ≥12 g/dl) | 0.412 | 0.158 |
Leucocyte (<11,000 vs. ≥11,000/mm3) | 0.829 | |
Platelet (<350,000 vs. ≥350,000/mm3) | 0.763 | 0.105 |
Sedimentation (<40 vs. ≥40 mm/h) | 0.524 | 0.116 |
Response to chemotherapy (yes vs. no) |
Significant P-values (<0.05) are highlighted in bold. NSCLC, non-small-cell lung cancer; SCLC, small-cell lung cancer; LDH, lactate dehydrogenase.
Survival estimates of patients analyzed according to age.
Age <60 years | Age ≥60 years | |||
---|---|---|---|---|
|
| |||
Variables | Median OS (weeks) | P-value | Median OS (weeks) | P-value |
Gender (female vs. male) | 49.7/53.8 | 0.923 | 37.8/49.1 | 0.465 |
Histology (NSCLC vs. SCLC) | 57.0/NR | 0.848 | 49.1/7.2 | |
Histology subtype (adenocarcinoma vs. other) | 49.7/57.0 | 0.850 | 62.1/30.8 | 0.072 |
Stage of NSCLC (non-metastatic vs. metastatic) | 57.0/41.8 | 62.1/29.8 | 0.192 | |
LDH (<450 vs. ≥450 IU/l) | NR/50.5 | 62.1/20.0 | ||
Hemoglobin (<12 vs. ≥12 g/dl) | NR/57.0 | 0.553 | NR/37.8 | 0.689 |
WBC (<11,000 vs. ≥11,000/mm3) | 57.0/NR | 0.554 | 49.1/37.8 | 0.660 |
Platelet (<350,000 vs. ≥350,000/mm3) | NR/57.0 | 0.493 | 49.1/NR | 0.230 |
Sedimentation (<40 vs. ≥40 mm/h) | NR/NR | 0.560 | 62.1/20.1 | 0.226 |
Response to chemotherapy (yes vs. no) | NR/49.7 | 0.817 | NR/20.1 | 0.378 |
Significant P-values (<0.05) are highlighted in bold. NR, not reached; OS, overall survival; NSCLC, non-small cell lung cancer; SCLC, small cell lung cancer; LDH, lactate dehydrogenase.